Application of demethylzeylasteral in preparation of medicine for resisting methicillin-resistant staphylococcus aureus
By using norzeralimal as the active ingredient, local application preparations, dressings and surface disinfectants have been developed, which solves the problems of limited coverage and adverse reactions of existing anti-MRSA drugs, and achieves safer and more effective MRSA treatment effects.
Patent Information
- Application Number
- CN202510700051.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-28
- Publication Date
- 2025-07-22
AI Technical Summary
Existing anti-MRSA drugs have limited coverage of other pathogens, and have severe adverse reactions and complex metabolic properties, with large individual differences and need to be improved or found for alternatives.
Using norzeramusaldehyde as an active ingredient, locally administered preparations, dressings, pharmaceutical compositions and surface disinfectants that are resistant to methicillin-resistant Staphylococcus aureus are developed, and effective inhibition of MRSA is achieved through multi-target synergistic action and sustained release materials.
It provides a safer, comprehensive and targeted MRSA treatment plan, which is cost-effective, reduces adverse reactions, and enhances the treatment effect and prognosis.
Smart Images
Figure CN120346212A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technology, and particularly to the application of demethylzeylasteral in the preparation of drugs against methicillin-resistant Staphylococcus aureus. Background Art
[0002] Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogenic bacterium that causes hospital infections and community infections. MRSA mainly acquires the mecA gene, which encodes a special penicillin-binding protein PBP2a. PBP2a has extremely low affinity for β-lactam antibiotics, thus enabling the bacteria to be resistant to a variety of β-lactam antibiotics including methicillin. In addition, MRSA can also develop resistance to other classes of antibiotics such as quinolones and aminoglycosides through other mechanisms, such as efflux pump systems and changes in cell membrane permeability, gradually becoming a multi-drug resistant bacterium.
[0003] MRSA spreads widely globally and is particularly common in hospital settings. It is one of the important pathogenic bacteria causing nosocomial infections and can lead to various severe infectious diseases such as pneumonia, sepsis, endocarditis, and wound infections. At the same time, community-acquired MRSA infections are also on the rise and are prone to outbreaks in areas with dense populations and relatively poor sanitary conditions, posing a huge challenge to public health. Although there are some drugs with certain antibacterial activity against MRSA, their coverage of other pathogenic bacteria is often limited. Some drugs for treating MRSA infections have relatively severe adverse reactions, are prone to causing renal impairment, may also show ototoxicity, bone marrow suppression, and long-term use may also cause peripheral neuropathy and optic neuropathy, etc. The metabolic characteristics of some anti-MRSA drugs are relatively complex, with large individual differences, and it is necessary to closely monitor the blood drug concentration to adjust the dosage, and there is an urgent need to improve or find alternative solutions.
[0004] In summary, finding a more effective, safe, comprehensive and targeted treatment for MRSA has important clinical significance and social value. Summary of the Invention
[0005] The purpose of the present invention is to provide the application of demethylzeylasteral in the preparation of drugs against methicillin-resistant Staphylococcus aureus, providing a new effective drug for the treatment of MRSA.
[0006] To achieve the above invention purpose, the present invention provides the following technical solutions: The present invention provides the application of demethylzeylasteral in the preparation of drugs against methicillin-resistant Staphylococcus aureus.
[0007] Preferably, the effective concentration of demethylzeylasteral in the drug is above 50 μM.
[0008] The present invention also provides a topically applied preparation for combating methicillin-resistant Staphylococcus aureus (MRSA), with demethylzeylasteral as the active ingredient.
[0009] Preferably, the topically applied preparation for combating MRSA is an ointment, gel, cream or spray.
[0010] The present invention also provides a dressing for combating MRSA, comprising demethylzeylasteral and a medical dressing matrix.
[0011] The present invention also provides the use of a pharmaceutical composition in the preparation of a drug for combating MRSA, wherein the pharmaceutical composition comprises demethylzeylasteral and an antibiotic.
[0012] The present invention also provides the use of a pharmaceutical composition in the preparation of a drug for combating MRSA, wherein the pharmaceutical composition comprises demethylzeylasteral and a sustained-release material.
[0013] The present invention also provides the use of a surface disinfectant in combating MRSA, wherein the surface disinfectant contains demethylzeylasteral; The surface disinfectant is a liquid or aerosol.
[0014] Preferably, the effective concentration of demethylzeylasteral in the surface disinfectant is above 50 μM.
[0015] Preferably, the surface disinfectant is a surface disinfectant dedicated to the medical environment.
[0016] Advantages of the present invention: The present invention has confirmed that demethylzeylasteral has the efficacy of combating MRSA and can directly inhibit the growth of MRSA. As a drug that has been widely used in the treatment of coronavirus infection and has a relatively rich source, its application in the treatment of MRSA will have better cost-effectiveness advantages and bring better treatment effects and prognoses to the majority of patients. Description of the Drawings
[0017] Figure 1 It is a bacteriostatic result diagram of demethylzeylasteral against MRSA; Figure 2 It is the test process of the minimum inhibitory concentration (MIC) of demethylzeylasteral against MRSA; Figure 3 It is the time-kill curve diagram of demethylzeylasteral against MRSA. Detailed Embodiments
[0018] The present invention provides the use of demethylzeylasteral in the preparation of a medicament against methicillin-resistant Staphylococcus aureus. Preferably, the effective concentration of demethylzeylasteral in the medicament is above 50 μM.
[0019] The present invention also provides a topically administered preparation against methicillin-resistant Staphylococcus aureus, with demethylzeylasteral as the active ingredient. In the present invention, the "topically administered preparation" refers to a pharmaceutical dosage form that directly acts on target areas such as the skin, mucosa, or wound surface through a non-systemic administration route, and its mechanism of action is to form effective antibacterial action at the infection site by locally penetrating or retaining and releasing the active ingredient.
[0020] Preferably, the topically administered preparation against methicillin-resistant Staphylococcus aureus is an ointment, gel, cream, or spray. Among them, the ointment using an oily matrix can achieve the dual functions of drug sustained release and skin barrier protection; the water-soluble matrix of the gel is suitable for exudative wounds and enhances drug permeability; the cream balances the hydrophilic and lipophilic properties through an emulsification system to improve the bioavailability of the drug; the spray achieves large-area coverage and rapid film formation through atomization and dispersion technology.
[0021] The present invention also provides a dressing against methicillin-resistant Staphylococcus aureus, comprising demethylzeylasteral and a medical dressing matrix. The medical dressing matrix includes but is not limited to hydrocolloid, alginate, or polyurethane foam material, which can load demethylzeylasteral by physical adsorption or chemical bonding, trigger drug controlled release when contacting wound exudate, and at the same time maintain a moist environment at the wound surface to enhance the destruction effect of antibacterial components on the MRSA biofilm.
[0022] The present invention also provides the use of a pharmaceutical composition in the preparation of a medicament against methicillin-resistant Staphylococcus aureus, wherein the pharmaceutical composition includes demethylzeylasteral and an antibiotic, and reduces the bacterial drug resistance mutation rate through multi-target synergistic action.
[0023] The present invention also provides the use of a pharmaceutical composition in the preparation of a medicament against methicillin-resistant Staphylococcus aureus, wherein the pharmaceutical composition includes demethylzeylasteral and a sustained-release material. The sustained-release material can preferably be poly(lactic-co-glycolic acid) (PLGA), chitosan microspheres, etc., and regulates the release kinetics of demethylzeylasteral by encapsulation or covalent coupling.
[0024] The present invention also provides the use of a surface disinfectant against methicillin-resistant Staphylococcus aureus, wherein the surface disinfectant contains demethylzeylasteral; the surface disinfectant is a liquid or aerosol. The aerosol form can enhance the permeability to complex surfaces with the aid of nano-scale atomized particles, and is particularly suitable for difficult-to-clean areas such as the seams of medical devices.
[0025] Preferably, the effective concentration of demethylzeylasteral in the surface disinfectant is above 50 μM.
[0026] Preferably, the surface disinfectant is a surface disinfectant specifically for medical environments to meet the sterilization requirements of high-risk areas in hospitals. It contains volatile organic solvents (such as ethanol) to accelerate drying and film formation, and pH buffers are added to maintain the chemical stability of demethylzeylasteral in an alkaline environment.
[0027] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.
[0028] Embodiment Pharmacodynamic evaluation of demethylzeylasteral against MRSA: Take the bacterial liquid (preserved in the laboratory) of Staphylococcus aureus ATCC43300 stored frozen, and streak inoculate it on the LB medium plate. Invert the inoculated plate and place it in an incubator, and culture it at 37 °C for 18 - 24 hours. Pick single colonies from the Staphylococcus aureus plate and inoculate them into 5 mL of LB, and culture them overnight with shaking at 37 °C and 180 r / min. Then dilute the overnight cultured bacterial liquid with fresh LB to about 1×10 6 CFU / mL as the experimental bacterial liquid.
[0029] Disk diffusion method: Use sterile forceps to pick up the disk soaked with demethylzeylasteral, and gently stick it on the surface of the plate containing the bacterial liquid. Invert the plate with the disk stuck and place it in an incubator, and culture it at 37 °C for 16 - 18 hours. After the culture is completed, take out the plate, observe and measure the size of the inhibition zone, as Figure 1 shown.
[0030] The MIC experiment steps for MRSA are as follows. Take the bacterial liquid in the logarithmic phase and dilute it with LB medium to 1×10 6 PFU / mL as the experimental bacterial liquid. Perform serial dilutions of demethylzeylasteral in a sterile 96-well microtiter plate. Add 400 μM of demethylzeylasteral to the first well, mix well, then aspirate 100 μL and transfer it to the second well, and so on for serial dilutions until the last well, and discard 100 μL. Then add 100 μL of the diluted bacterial liquid to each well. At the same time, set up a positive control well (containing only the bacterial liquid and the medium) and a negative control well (containing only the medium). Incubate the 96-well microtiter plate at 37 °C for 24 h. After the culture is completed, add 20 μL of 0.2% resazurin solution to each well, gently shake and mix well, and then continue to incubate in a 37 °C incubator for 1 - 2 hours. The lowest antimicrobial drug concentration that completely inhibits bacterial growth (the solution is blue) is the MIC of the strain to demethylzeylasteral, as Figure 2 shown.
[0031] It can be seen from Figure 2 that the minimum inhibitory concentration (MIC) of demethylzeylasteral against MRSA is 50 μM.
[0032] The experimental procedure of the time-kill curve of MRSA is as follows: Take the bacterial solution in the logarithmic phase, dilute it to 1×10^6 PFU / mL with LB medium as the experimental bacterial solution. Take 4 sterile test tubes, add 2 MIC and MIC demethylzeylasteral drug solutions respectively, and then add 10 mL of the diluted bacterial solution to each test tube. At the same time, set up positive control tubes and negative control tubes. Place the above test tubes in a shaker at 37°C and take samples at different time points of 0, 5, 10, 12, 14, 20, 24, and 48 hours after cultivation, and measure the OD value of the sampled bacterial solution at a wavelength of 600 nm, as Figure 3 shown.
[0033] It can be seen from Figure 3 that within 14 hours after adding demethylzeylasteral, the relative OD value is below 0.5, indicating that demethylzeylasteral has an obvious inhibitory or killing effect on the growth of MRSA during this period.
[0034] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.
Claims
1. Use of demethylzeylasteral in the preparation of a drug against methicillin-resistant Staphylococcus aureus.
2. The application according to claim 1, wherein The effective concentration of demethylzeylasteral in the drug is above 50 μM.
3. A topically applied preparation against methicillin-resistant Staphylococcus aureus, characterized in that, Using demethylzeylasteral as the active ingredient.
4. The topically administered preparation against methicillin-resistant Staphylococcus aureus according to claim 3, characterized in that, The topical preparation against methicillin-resistant Staphylococcus aureus is an ointment, gel, cream or spray.
5. An anti-methicillin-resistant Staphylococcus aureus dressing, characterized in that, Containing demethylzeylasteral and a medical dressing matrix.
6. Use of a pharmaceutical composition in the preparation of a medicament against methicillin-resistant Staphylococcus aureus, characterized in that, The pharmaceutical composition includes demethylzeylasteral and an antibiotic.
7. Use of a pharmaceutical composition in the preparation of a medicament against methicillin-resistant Staphylococcus aureus, characterized in that, The pharmaceutical composition includes demethylzeylasteral and a sustained-release material.
8. Use of a surface disinfectant in combating methicillin-resistant Staphylococcus aureus, characterized in that, The surface disinfectant contains demethylzeylasteral; The surface disinfectant is a liquid or an aerosol.
9. The application according to claim 8, characterized in that, The effective concentration of demethylzeylasteral in the surface disinfectant is above 50 μM.
10. The application according to claim 8, characterized in that, The surface disinfectant is a surface disinfectant dedicated to the medical environment.